HIV-1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development.

@article{citeulike:3177639, abstract = {Damaged DNA binding protein DDB1 bridges an estimated more than 90 WD40 repeat (DWD) to the CUL4-ROC1 catalytic core to constitute a potentially large number of E3 ligase complexes. Among these DWD proteins is HIV-1 Vpr-binding protein VprBP, whose cellular function has yet to be characterized, but has recently been found to mediate Vpr-induced G2 cell cycle arrest. We demonstrate here that VprBP binds stoichiometrically with DDB1 through its WD40 domain and through DDB1 to CUL4A, subunits of COP9/signalsome and DDA1. The steady state level of VprBP remains constant during interphase and decreases during mitosis. VprBP binds to chromatin in a DDB1-independent and cell cycle dependent manner, increasing from early S through G2 before decreasing to undetectable levels in mitotic and G1 cells. Silencing VprBP reduced the rate of DNA replication, blocked cells from progressing through the S-phase, and inhibited proliferation. VprBP ablation in mice results in early embryonic lethality. Conditional deletion of the VprBP gene in mouse embryonic fibroblasts results in severely defective progression through S-phase and subsequent apoptosis. Our studies identify a previously unknown function of VprBP in S-phase progression and suggest the possibility that HIV-1 Vpr may divert an ongoing chromosomal replication activity to facilitate viral replication.}, address = {Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, Department of Pathology and Laboratory Medicine, Program in Molecular Biology and Biotechnology, University of North Carolina School of Medicine, Chapel Hill, NC 27599.}, author = {McCall, Chad M M. and Miliani de Marval, Paula L L. and Chastain, Paul D D. and Jackson, Sarah C C. and He, Yizhou J J. and Kotake, Yojiro and Cook, Jeanette Gowen G. and Xiong, Yue }, citeulike-article-id = {3177639}, doi = {http://dx.doi.org/10.1128/MCB.00232-08}, issn = {1098-5549}, journal = {Molecular and cellular biology}, keywords = {hiv, replication, vpr}, month = {July}, posted-at = {2008-09-01 08:41:16}, priority = {2}, title = {HIV-1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development.}, url = {http://dx.doi.org/10.1128/MCB.00232-08}, year = {2008} }

TY - JOUR ID - citeulike:3177639 L3 - citeulike-article-id:3177639 N2 - Damaged DNA binding protein DDB1 bridges an estimated more than 90 WD40 repeat (DWD) to the CUL4-ROC1 catalytic core to constitute a potentially large number of E3 ligase complexes. Among these DWD proteins is HIV-1 Vpr-binding protein VprBP, whose cellular function has yet to be characterized, but has recently been found to mediate Vpr-induced G2 cell cycle arrest. We demonstrate here that VprBP binds stoichiometrically with DDB1 through its WD40 domain and through DDB1 to CUL4A, subunits of COP9/signalsome and DDA1. The steady state level of VprBP remains constant during interphase and decreases during mitosis. VprBP binds to chromatin in a DDB1-independent and cell cycle dependent manner, increasing from early S through G2 before decreasing to undetectable levels in mitotic and G1 cells. Silencing VprBP reduced the rate of DNA replication, blocked cells from progressing through the S-phase, and inhibited proliferation. VprBP ablation in mice results in early embryonic lethality. Conditional deletion of the VprBP gene in mouse embryonic fibroblasts results in severely defective progression through S-phase and subsequent apoptosis. Our studies identify a previously unknown function of VprBP in S-phase progression and suggest the possibility that HIV-1 Vpr may divert an ongoing chromosomal replication activity to facilitate viral replication. JF - Molecular and cellular biology SN - 1098-5549 AD - Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, Department of Pathology and Laboratory Medicine, Program in Molecular Biology and Biotechnology, University of North Carolina School of Medicine, Chapel Hill, NC 27599. TI - HIV-1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development. KW - hiv KW - replication KW - vpr AU - McCall, Chad M AU - Miliani de Marval, Paula L AU - Chastain, Paul D AU - Jackson, Sarah C AU - He, Yizhou J AU - Kotake, Yojiro AU - Cook, Jeanette Gowen AU - Xiong, Yue PY - 2008/07/07/ UR - http://dx.doi.org/10.1128/MCB.00232-08 ER -